PROJECT SUMMARY The Tri-Institutional MD-PhD Program is a joint undertaking of Weill Cornell Medicine (WCM), The Rockefeller University (RU), and the Sloan Kettering Institute for Cancer Research (SKI). Its mission is to train biomedical investigators who: on the one hand, have advanced understanding of biomedical science and a mastery of contemporary research skills, which will allow them to undertake fundamental studies to elucidate basic biological processes pertaining to human disease; and, on the other hand, are well grounded in human biology, pathobiology and clinical medicine, which will equip them to transfer advances in basic research to the understanding, prevention, and treatment of human disease. The three institutions operate three graduate schools: Weill Cornell Graduate School of Medical Sciences (WCGS), a joint undertaking between WCM and SKI; the David Rockefeller Graduate School at RU; and the Gerstner Graduate School of Biomedical Sciences (GSK) at SKI. The Tri-Institutional MD-PhD Program was formed in 1991, when two independent MD-PhD Programs, the WCM-RU Program and the WCM-WCGS Program, were joined to form the present program. GSK became part of the Program in 2009. MSTP trainees complete all requirements for the MD degree at WCM. They receive their PhD training in research laboratories in the three research institutions and receive their PhD degree from GSK, RU or WCGS. Accepted trainees arrive in early July before the start of medical school. During the first two years in the Program they complete their medical school course, take two graduate level courses designed for MD-PhD students, and complete three research rotations (in three different laboratories) before they settle into their thesis laboratory. When the students choose a research laboratory they enroll in the graduate school with which their thesis mentor is associated. The graduate course and thesis requirements are comparable for all MD-PhD students, irrespective of the graduate school in which they are matriculated?and the students can cross register and take courses for credit in any of the graduate schools. At the end of their research training, after they have defended their thesis, the students return to complete their clinical training at WMC. The present application requests funds to continue MD-PhD training at the three institutions beyond Year 45 (the predecessor WCMC-RU Program was formed in 1972; it received NIH funding in 1974). In its current iteration, the Program brings together faculty in more than 250 independent research laboratories. 379 MD- PhDs have graduated from the Tri-Institutional MD-PhD Program and its predecessors; currently there are 137 students in the Program. The current trainees come from 55 undergraduate schools. Their average GPA is 3.75. 94% of the graduates pursue post-graduate clinical training; of the 305 graduates who have completed their training, 258 (85%) have appointments in medical schools, research institutes or biotech/pharma.